Anthony Thomas G, Polley Spencer D, Vogler Alfried P, Conway David J
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St., London WC1E 7HT, UK.
Mol Biochem Parasitol. 2007 Dec;156(2):117-23. doi: 10.1016/j.molbiopara.2007.07.008. Epub 2007 Jul 20.
Targeted disruption of particular members of the Plasmodium 6-cys protein gene family, including Ps47, Ps48/45 and Ps230, is known to dramatically affect parasite fertility. Because loci critical to fertility in many eukaryote species have been shown to be under strong positive selection, we examined sequence variation in four members of the 6-cys protein gene family in Plasmodium falciparum (Pfs36, Pfs38, Pfs47 and Pfs48/45) to determine whether genetic variation in these loci may be of functional significance. Sequence polymorphism among 11 laboratory isolates of P. falciparum was compared with divergence from the respective orthologues in the closely related species P. reichenowi, showing an almost significant skew towards within-species non-synonymous polymorphism in Pfs47 and Pfs48/45 (by the McDonald-Kreitman test) but clearly non-significant results for Pfs36 and Pfs38. A preliminary analysis of Pfs47 sequence polymorphism in field isolates of P. falciparum showed exceptionally high fixation indices (F(ST)) among geographically distinct populations, similar to results seen previously for Pfs48/45. Therefore, both Pfs47 and Pfs48/45 were further analysed by sequencing polymorphic parts of the genes from a Tanzanian population sample of oocysts (a means of analysing diploid genotypes). Both genes displayed higher inbreeding coefficients (F(IS)) compared with the average of 11 unlinked microsatellite loci. These results suggest that allelic variation in these two genes may be functionally significant in influencing mating interactions, a hypothesis that could be tested by fertilization experiments with targeted allelic replacement.
已知对疟原虫6 - 半胱氨酸蛋白基因家族的特定成员（包括Ps47、Ps48/45和Ps230）进行靶向破坏会显著影响寄生虫的繁殖力。由于已表明许多真核生物物种中对繁殖力至关重要的基因座处于强烈的正选择之下，我们研究了恶性疟原虫6 - 半胱氨酸蛋白基因家族的四个成员（Pfs36、Pfs38、Pfs47和Pfs48/45）中的序列变异，以确定这些基因座中的遗传变异是否可能具有功能意义。将11个恶性疟原虫实验室分离株之间的序列多态性与密切相关物种赖氏疟原虫中各自直系同源物的差异进行比较，结果显示Pfs47和Pfs48/45中种内非同义多态性几乎呈显著偏态（通过麦克唐纳 - 克里特曼检验），但Pfs36和Pfs38的结果明显不显著。对恶性疟原虫野外分离株中Pfs47序列多态性的初步分析表明，在地理上不同的群体中固定指数（F(ST)）异常高，这与之前在Pfs48/45中看到的结果相似。因此，通过对来自坦桑尼亚卵囊群体样本（一种分析二倍体基因型的方法）的基因多态性部分进行测序，对Pfs47和Pfs48/45进行了进一步分析。与11个不连锁微卫星基因座的平均值相比，这两个基因均显示出更高的近交系数（F(IS)）。这些结果表明，这两个基因中的等位基因变异可能在影响交配相互作用方面具有功能意义，这一假设可通过靶向等位基因替换的受精实验进行检验。
